§If iron accumulation has already occurred then overall survival drops to around 60%

§Interestingly if the patient has had more than 100 units of blood the chances of rejection fall and a redcuced intensity regime may be used

§Bone marrow may be preferred rather than peripheral blood to reduce the risk of GVHD

§Patients often have mixed chimerism

§Sickle cell disease

§Difficulty predicting clinical course for the patients

§Children with significant risk often not identified until they have end organ damage

§Difficult to identify suitable unaffected sibling donors (only available for 14% of patients in one study)

§Over 90% survival with over 85% being disease free

§Results from a Belgian study suggest that if the patients are transplanted very early (<4 blood transfusions) they have a better outcome.

§Mixed chimersism develops in some patients (similar to thalssaemia)

Immune deficiency

§New borns identified as at high risk of SCID should be isolated at birth – infection increases the TRM

§Definitive diagnosis is important so that the natural history of the disease can be established and the intensity of the transplant conditioning tailored (determined by lymphocyte and NK cell function)

§In some forms of SCIDS such as Jak3 deficiency the patient is unable to reject stem cells and a simple infusion is all that is required

§However often don’t regain B cell function unless there is chemotherapy given

§Survival best for matched sibling transplants with a 70-100% survival

§Falls to 50% when there is no sibling donor

§Either cord transplant (always CMV and EBV neg) or a hapling allograft from one of the parents

Metabolic disorders

§Role of transplant varies with the disorder (not effective for Niemann-Pick for example) but others such as Hurler and Hunter syndromes have been successfully treated with SCT.

§In some cases donor heterozygosity will not cure the disease (making transplant from the parents / siblings difficult)

§Possible to do IVF with embryos lacking the mutation and being HLA identical

Paediatric solid tumours

§Better outcome in neuroblastoma and Ewing’s sarcoma with autografting

Solid tumours

§Renal carcinoma – allografting may be helpful as may be susceptible to graft verses tumour effect

§Breast cancer

§Metastatic cancer - high dose therapy with autologous stem cell therapy does not seem to be of benefit.

§Dutch study has suggested that very high risk subsets (stage II or III disease with 10 or more positive lymph nodes) do better with autologous SCT (61 v 51% relapse free survival)

General transplant issues

Venoocclusive disease

§10-60% of patients

§Chemotherapy induced damage to endothelial cells, sinusoids and hepatocytes in the area surrounding terminal hepatic venules.